Sedaris currently lives in the Horsham District of West Sussex, England, with his longtime partner Hugh Hamrick, whom Sedaris mentions in a number of his stories.[21] Sedaris describes them as the "sort of couple who wouldn't get married".[22][23] He enjoys collecting litter in the local area, where he is known as "Pig Pen", and has a garbage truck named after him.[24][25]

While working odd jobs across Raleigh, Chicago, and New York City, Sedaris was discovered in a Chicago club by radio host Ira Glass; Sedaris was reading a diary he has kept since 1977. Glass asked him to appear on his weekly local program, The Wild Room.[26] Sedaris said, "I owe everything to Ira ... My life just changed completely, like someone waved a magic wand."[27] Sedaris' success on The Wild Room led to his National Public Radio debut on December 23, 1992, when he read a radio essay on Morning Edition titled "SantaLand Diaries", which described his purported experiences as an elf at Macy's department store during Christmas in New York.

"SantaLand Diaries" was a success with listeners,[28] and made Sedaris what The New York Times called "a minor phenomenon".[26] He began recording a monthly segment for NPR based on his diary entries, edited and produced by Glass, and signed a two-book deal with Little, Brown and Company.[26] In 1993, Sedaris told The New York Times he was publishing his first book, a collection of stories and essays, and had 70 pages written of his second book, a novel "about a man who keeps a diary and whom Mr. Sedaris described as 'not me, but a lot like me'".[26]

In April 2001, Variety reported Sedaris had sold the Me Talk Pretty One Day film rights to director Wayne Wang, who was adapting four stories from the book for Columbia Pictures.[16][32] Wang had completed the script and begun casting when Sedaris asked to "get out of it", after he and his sister worried how their family might be portrayed. He wrote about the conversation and its aftermath in the essay "Repeat After Me". Sedaris recounted that Wang was "a real prince ... I didn't want him to be mad at me, but he was so grown up about it. I never saw how it could be turned into a movie anyway."[33]

In September 2007, a new Sedaris collection was announced for publication on June 3, 2008.[7] The collection's working title was All the Beauty You Will Ever Need, but Sedaris retitled it Indefinite Leave to Remain and finally settled on the title When You Are Engulfed in Flames.[6][35] Although at least one news source assumed the book would be fables,[7] Sedaris said in October 2007 that the collection might include a "surprisingly brief story about [his] decision to quit smoking ... along with stories about a Polish crybaby, throwing shit in a paraplegic's yard, chimpanzees at a typing school, and people visiting [him] in France."[6]

In April 2010, BBC Radio 4 aired Meet David Sedaris, a four-part series of essays which Sedaris read before a live audience.[37] A second series of 6 programmes began airing on BBC Radio 4 Extra on June 13, 2011, with third series beginning on September 30, 2012.[38]

In 2007, in an article in The New Republic, Alexander S. Heard stated that much of Sedaris' work is insufficiently factual to justify being marketed as nonfiction.[43] Several published responses to Heard's article argued that Sedaris' readers are aware that his descriptions and stories are intentionally exaggerated and manipulated to maximize comic effect,[44] while others used the controversy as a springboard for discussing the liberties publishers are willing to take when calling books 'nonfiction'.[45]

Subsequently, in the wake of a controversy involving Mike Daisey's dramatizing and embellishing his personal experiences at Chinese factories, during an excerpt from his theatrical monologue for This American Life, new attention has been paid to the veracity of Sedaris' nonfiction stories. NPR will label stories from Sedaris, such as "SantaLand Diaries", as fiction, while This American Life will fact check stories to the extent that memories and long-ago conversations can be checked.[46]The New Yorker already subjects nonfiction stories written for that magazine to its comprehensive fact-checking policy.[47]

Sedaris also co-authored Incident at Cobbler's Knob, presented and produced by David Rockwell at the Lincoln Center Festival. Sets for those performances were designed by Sedaris' longtime partner, Hugh Hamrick, who also directed two of them, The Book of Liz and Incident at Cobbler's Knob.[citation needed]

Sedaris and his sister Amy shared "The Talent Family" credit on the latter's short-lived sketch comedy show Exit 57, while David was a contributing writer.[citation needed]